title: Thiosulfate: a readily accessible source of hydrogen sulfide in oxygen sensing.
abstract: H2S derived from organic thiol metabolism has been proposed serve as an oxygen sensor in a variety of systems because of its susceptibility to oxidation and its ability to mimic hypoxic responses in numerous oxygen-sensing tissues. Thiosulfate, an intermediate in oxidative H2S metabolism can alternatively be reduced and regenerate H2S. We propose that this contributes to the H2S-mediated oxygen-sensing mechanism. H2S formation from thiosulfate in buffers and in a variety of mammalian tissues and in lamprey dorsal aorta was examined in real time using a polarographic H2S sensor. Inferences of intracellular H2S production were made by examining hypoxic pulmonary vasoconstriction (HPV) in bovine pulmonary arteries under conditions in which increased H2S production would be expected and in mouse and rat aortas, where reducing conditions should mediate vasorelaxation. In Krebs-Henseleit (mammalian) and Cortland (lamprey) buffers, H2S was generated from thiosulfate in the presence of the exogenous reducing agent, DTT, or the endogenous reductant dihydrolipoic acid (DHLA). Both the magnitude and rate of H2S production were greatly increased by these reductants in the presence of tissue, with the most notable effects occurring in the liver. H2S production was only observed when tissues were hypoxic; exposure to room air, or injecting oxygen inhibited H2S production and resulted in net H2S consumption. Both DTT and DHLA augmented HPV, and DHLA dose-dependently relaxed precontracted mouse and rat aortas. These results indicate that thiosulfate can contribute to H2S signaling under hypoxic conditions and that this is not only a ready source of H2S production but also serves as a means of recycling sulfur and thereby conserving biologically relevant thiols.
authors.affiliation: Indiana University School of Medicine-South Bend Center, South Bend, Indiana; and.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Olson
authors.forename: Eric R
authors.initials: ER
authors.lastname: Deleon
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.forename: Kevin
authors.initials: K
authors.lastname: Hurley
authors.forename: Victor
authors.initials: V
authors.lastname: Sadauskas
authors.forename: Catherine
authors.initials: C
authors.lastname: Batz
authors.forename: Gilbrian F
authors.initials: GF
authors.lastname: Stoy
mesh_terms: D000818:Animals; D002417:Cattle; D015687:Cell Hypoxia / Q000502:physiology; D005260:Female; D006862:Hydrogen Sulfide / Q000737:chemistry* / Q000378:metabolism*; D007798:Lampreys; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D013045:Species Specificity; D013885:Thiosulfates / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D013885:Thiosulfates; D010100:Oxygen; D006862:Hydrogen Sulfide
keywords: gasotransmitter; mitochondria; oxygen sensing